Design of bacteria-agglutinating peptides derived from parotid secretory protein, a member of the bactericidal/permeability increasing-like protein family.
Parotid secretory protein (PSP) (SPLUNC2), a potential host-defense protein related to bactericidal/permeability-increasing protein (BPI), was used as a template to design antibacterial peptides. Based on the structure of BPI, new PSP peptides were designed and tested for antibacterial activity. The peptides did not exhibit significant bactericidal activity or inhibit growth but the peptide GL-13 induced bacterial matting, suggesting passive agglutination of bacteria. GL-13 was shown to agglutinate the Gram negative bacteria Pseudomonas aeruginosa and Aggregatibacter (Actinobacillus) actinomycetemcomitans, Gram positive Streptococcus gordonii and uncoated sheep erythrocytes. Bacterial agglutination was time and dose-dependent and involved hydrophobic interactions. Variant forms of GL-13 revealed that agglutination also depended on the number of amine groups on the peptide. GL-13 inhibited the adhesion of bacteria to plastic surfaces and the peptide prevented the spread of P. aeruginosa infection in a lettuce leaf model, suggesting that GL-13 is active in vivo. Moreover, GL-13-induced agglutination enhanced the phagocytosis of P. aeruginosa by RAW 264.7 macrophage cells. These results suggest that GL-13 represents a class of antimicrobial peptides, which do not directly kill bacteria but instead reduce bacterial adhesion and promote agglutination, leading to increased clearance by host phagocytic cells. Such peptides may cause less bacterial resistance than traditional antibiotic peptides.
Gorr
Sven-Ulrik
SU
Oral Health and Systemic Disease Research Group, Department of Periodontics, Endodontics and Dental Hygiene, University of Louisville School of Dentistry, Room 331, 501 S Preston Street, Louisville, Kentucky 40292, USA. sven.gorr@louisville.edu
Sotsky
Julie B
JB
Shelar
Anuradha P
AP
Demuth
Donald R
DR
D000371:Agglutination / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D018545:Lactuca / Q000187:drug effects / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000494:pharmacology*; D012756:Sheep
C045623:BPIFA2 protein, human; D012471:Salivary Proteins and Peptides